Opto-fluidics is a recently emerging field that aims to merge the available toolset of optics and microfluidics to create more flexible and reconfigurable optical devices with novel functionalities that can provide a better fit to especially lab-on-a-chip platforms. The cost-effectiveness and compactness of lab-on-a-chip devices when combined with throughput and sensitivity have already enabled powerful solutions to a wide range of biomedical problems. Creation of new opto-fluidic technologies would further enhance the performance and functionality of existing lab-on-a-chip platforms, and toward this end various opto-fluidic devices have been demonstrated including tunable lasers, lenses, waveguides and sensors. Microfluidics enabled on-chip digital microscopy could especially be important for global health problems to assist diagnosis of disease (e.g., malaria, tuberculosis) in remote locations, and holds significant promise not only for point-of-care operation but also for telemedicine applications.
Opto-Fluidic Microscopy (OFM) is a microfluidic imaging concept that came out of this emerging field, which aims to image objects flowing within a micro-fluidic channel without the use of any lenses. These OFM systems abandon conventional microscope design, which requires expensive lenses and large space to magnify the images, and instead uses microfluidic flow to deliver specimens across array(s) of micrometer-sized apertures defined on a metal-coated CMOS sensor to generate direct projection images. For example, such as system is disclosed in Cui et al., Lensless high-resolution on-chip opto-fluidic microscopes for Caenorhabditis elegans and cell imaging. Proc. Natl. Acad. Sci. 105, 10670-10675 (2008). Thus, conventional OFM designs rely on a digital sensor-array, such as a complementary metal-oxide semiconductor (CMOS) or a charge-coupled device (CCD) chip, which is placed directly underneath the micro-fluidic channel to sample the transmitted light that passes through the flowing object. To overcome the limited spatial resolution dictated by relatively large pixel size at the sensor-chip, OFM utilizes a slanted micro or nano-sized aperture array fabricated on the active area of the sensor, such that under controlled flow conditions, the spatial resolution becomes independent of the pixel size yielding high-resolution reconstructed digital images. OFM thus has additional manufacturing complexity given the need for the aperture array atop of the imaging sensor.
OFM images the transmission intensity of the objects specifically at the aperture plane (within 1-2 μm depth) and cannot yet achieve depth focusing or backward wave propagation as it lacks complex wave information. Because of this, the microfluidic channel of OFM-based devices needs to be fabricated very close to the active region of the CMOS or CCD sensor which necessitates the mechanical removal of the protective cover glass of the sensor. Another limitation of OFM is that it demands that the position of the object be constant with respect to the microchannel cross-section. Often, however, cells or particles within a microfluidic flowing environment experience lateral shifting during flow.
An on-chip imaging system and method that does not require fabrication of complicated apertures on a chip, nor demands distortion-free motion of the objects within the microchannel would be particularly useful. This would significantly improve the practical implementations of lens-free opto-fluidic on-chip imaging, while also significantly increasing the light collection efficiency.